CELANCE

Main information

  • Trade name:
  • CELANCE Tablets 50 Microgram
  • Dosage:
  • 50 Microgram
  • Pharmaceutical form:
  • Tablets
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CELANCE Tablets 50 Microgram
    Ireland
  • Language:
  • English

Status

  • Source:
  • HPRA - Health Products Regulatory Authority - Ireland
  • Authorization number:
  • PA0047/073/001
  • Authorization date:
  • 18-10-1993
  • Last update:
  • 14-10-2016

Summary of Product characteristics: dosage, interactions, side effects

IRISHMEDICINESBOARDACT1995,asamended

MedicinalProducts(ControlofPlacingontheMarket)Regulations,2007,asamended

PA0047/073/001

CaseNo:2085192

TheIrishMedicinesBoardinexerciseofthepowersconferredonitbytheabovementionedRegulationsherebygrantsto

EliLillyandCompanyLimited

LillyHouse,PriestleyRoad,Basingstoke,Hampshire,RG249NL,UnitedKingdom

anauthorisation,subjecttotheprovisionsofthesaidRegulations,inrespectoftheproduct

Celance50microgramtablets

theparticularsofwhicharesetoutintheattachedSchedule.Theauthorisationisalsosubjecttothegeneralconditionsasmaybespecifiedin

thesaidRegulationsaslistedonthereverseofthisdocument.

Thisauthorisation,unlesspreviouslyrevoked,shallcontinueinforcefrom07/07/2010.

SignedonbehalfoftheIrishMedicinesBoardthis

________________

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PartII

SummaryofProductCharacteristics

1NAMEOFTHEMEDICINALPRODUCT

Celance50microgramtablets.

2QUALITATIVEANDQUANTITATIVECOMPOSITION

Eachtabletcontainspergolidemesilateequivalentto50microgramsofpergolide.

Excipient:Contains287mglactosemonohydratepertablet.

Forafulllistofexcipients,seesection6.1.

3PHARMACEUTICALFORM

Tablet.

Ivory,modifiedrectangleshapedtablet,scoredandmarked“Lilly4131”.

4CLINICALPARTICULARS

4.1TherapeuticIndications

PergolidemesilateisanergotderivativedopaminereceptoragonistatD

,D

andD

receptorsites.

Iftreatmentwithadopamineagonistisbeingconsidered,pergolidemesilateisindicatedassecondlinetherapyin

patientswhoareintolerantorfailtreatmentwithanon-ergotcompound,asmonotherapy,orasadjunctivetreatmentto

levodopainthemanagementofthesignsandsymptomsofParkinson'sdisease.

Treatmentshouldbeinitiatedunderspecialistsupervision.Thebenefitofcontinuedtreatmentshouldberegularly

reassessedtakingintoaccounttheriskoffibroticreactionsandvalvulopathy(seesections4.3,Contraindications4.4,

Specialwarningsandprecautionsforuseand4.8,Undesirableeffects).

4.2Posologyandmethodofadministration

Fororaladministrationtoadultsonly.

Dosesofpergolidemesilateabove3mg/day(3000micrograms/day)arenottobeusedeitherasmonotherapyorwith

levodopaduetotheriskoffibroticcardiacvalvulopathy(Seesection4.4,SpecialwarningsandPrecautionsforuse)

thatmightincreaseinfrequencywithgreaterdailydoseandorcumulativeexposure.Howevervalvulopathyand

fibroticreactionshavebeenreportedduringtreatmentwithpergolideatavarietyofdoseslessthan3mg/day.

Adjunctivetreatment

Administrationofpergolidemesilateshouldbeinitiatedwithadailydosageof50microgramsforthefirst2days.The

dosageshouldthenbegraduallyincreasedby100or150micrograms/dayeverythirddayoverthenext12daysof

therapy.Thedosagemaythenbeincreasedby250micrograms/dayeverythirddayuntilanoptimaltherapeuticdosage

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Pergolidemesilateisusuallyadministeredindivideddoses3timesperday.Duringdosagetitration,thedosageof

concurrent1-dopamaybecautiouslydecreased.

Inclinicalstudies,themeantherapeuticdailydosageofpergolidemesilatewas3mg/day(3000micrograms/day).The

averageconcurrentdailydosageof1-dopa/carbidopa(expressedas1-dopa)wasapproximately650mg/day.

Monotherapy

Thefollowingtitrationshouldbeusedforinitiationofpergolideasmonotherapy:

Afterday30,thedailydoseshouldbeincreasedbyatmost250microgramstwiceaweekuntilanoptimaltherapeutic

responseisachievedbutnottoexceed3mg/day.Pergolidemesilateisusuallyadministeredindivideddoses3timesper

day.

Inclinicalstudiesofpergolideasmonotherapy,themeandosewas2100microgramsperdayat3monthsand2510

microgramsperdayat1yearoftreatment.

Domperidonemaybeusedatrecommendeddosesatinitiationoftreatmenttominimiseanygastro-intestinalsymptoms

experienced.

Aswithotherdopamineagonists,pergolideshouldbediscontinuedgradually.

Children:Safetyandeffectivenesshavenotbeenestablished.

4.3Contraindications

Hypersensitivitytothisdrugorotherergotderivatives.

Historyoffibroticdisorders.

Evidenceofcardiacvalvulopathyasdeterminedbypre-treatmentechocardiography.

4.4Specialwarningsandprecautionsforuse

FibrosisandCardiacValvulopathyandpossiblyrelatedclinicalphenomena

Fibroticandserosalinflammatorydisorderssuchaspleuritis,pleuraleffusion,pleuralfibrosis,pulmonaryfibrosis,

pericarditis,pericardialeffusion,cardiacvalvulopathyinvolvingoneormorevalves(aortic,mitralandtricuspid)or

retroperitonealfibrosishaveoccurredafterprolongedusageofergotderivativeswithagonistactivityattheserotonin

5HT2Breceptor,suchaspergolide.Insomecases,symptomsormanifestationsofcardiacvalvulopathyimprovedafter

Day Morning Noon Evening TotalDosage

50micrograms 50micrograms

2-4 50micrograms 50micrograms 100micrograms

50micrograms 50micrograms 100micrograms 200micrograms

8-10 100micrograms 100micrograms 100micrograms 300micrograms

11-13 100micrograms 150micrograms 150micrograms 400micrograms

14-17 200micrograms 200micrograms 200micrograms 600micrograms

18-21 250micrograms 250micrograms 250micrograms 750micrograms

22-24 500micrograms 250micrograms 250micrograms 1000micrograms

25-27 500micrograms 500micrograms 250micrograms 1250micrograms

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Thereisevidencethathigherdoseand/orcumulativeexposureareriskfactorsfordevelopmentofvalvularpathology.

However,valvulopathyandfibroticreactionshavebeenreportedduringtreatmentwithpergolideatdoseslessthan0.5

mg/day.

Beforeinitiatingtreatment:

Allpatientsmustundergoacardiovascularevaluation,includingechocardiogram,toassessthepotentialpresenceof

asymptomaticvalvulardisease.Inpatientswithvalvularregurgitation,itisnotknownwhetherpergolidetreatment

mightworsentheunderlyingdisease.Iffibroticvalvulardiseaseisdetected,thepatientshouldnotbetreatedwith

pergolide(seeSection4.3,Contraindications)

Itisalsoappropriatetoperformbaselineinvestigationsoferythrocytesedimentationrateorotherinflammatory

markers,lungfunction/chestX-rayandrenalfunctionpriortoinitiationoftherapy.

Duringtreatment:

Fibroticdisorderscanhaveaninsidiousonsetandpatientsshouldberegularlymonitoredforpossiblemanifestationsof

progressivefibrosis.

Therefore,duringtreatmentattentionshouldbepaidtothesignsandsymptomsof:

Pleuro-pulmonarydisease,suchasdyspnoea,shortnessofbreath,persistentcoughorchestpain.

Renalinsufficiencyorureteral/abdominalvascularobstructionthatmayoccurwithpainintheloin/flankand

lowerlimboedemaaswellasanypossibleabdominalmassesortendernessthatmayindicateretroperitoneal

fibrosis

Cardiacfailure;casesofvalvularandpericardialfibrosishaveoftenmanifestedascardiacfailure.Therefore,

valvularfibrosis(andconstrictivepericarditis)shouldbeexcludedifsuchsymptomsoccur.

Clinicaldiagnosticmonitoringfordevelopmentofvalvulardiseaseorfibrosis,asappropriate,isessential.Following

treatmentinitiation,thefirstechocardiogramshouldoccurwithin3-6months,thereafter,thefrequencyof

echocardiographicmonitoringmustbedeterminedbyappropriateindividualclinicalassessmentwithparticular

emphasisontheabove-mentionedsignsandsymptoms,butmustoccuratleastevery6to12months.

Pergolideshouldbediscontinuedifanechocardiogramrevealsneworworsenedvalvularregurgitation,valvular

restrictionorvalveleafletthickening.(seesection4.3,Contraindications)Theneedforotherclinicalmonitoring(e.g.,

physicalexamination,includingcardiacauscultation,x-ray,CTscan)shouldbedeterminedonanindividualbasis.

Additionalappropriateinvestigationssuchaserythrocytesedimentationrateandserumcreatininemeasurementsshould

beperformedifnecessarytosupportadiagnosisofafibroticdisorder.

EndocrineEffects

Asymptomcomplexresemblingtheneurolepticmalignantsyndrome(NMS)(characterisedbyelevatedtemperature,

muscularrigidity,alteredconsciousnessandautonomicinstability),withnootherobviousaetiology,hasbeenreported

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Hypotension

Patientsandtheirfamiliesshouldbeinformedofthecommonadverseconsequencesoftheuseofpergolidemesilate

andtheriskofhypotension.

Patientsshouldbewarnedtobegintherapywithlowdosesandtoincreasedosageincarefullyadjustedincrementsover

aperiodof3to4weeks(seesection4.2,Posologyandmethodofadministration)tominimisetheriskofsymptomatic

orthostaticorposturalhypotensionand/orsustainedhypotension.Withgradualdosagetitration,tolerancetothe

hypotensionusuallydevelops(seesection4.5,Interactionswithothermedicinalproductsandotherformsof

interaction).

HallucinationsandPsychosisandrelatedevents

Hallucinationsareknowntobeassociatedwithdopamineagonistsandlevodopatreatment.Incontrolledtrials,

pergolidemesilatewithl-dopacausedhallucinosisinabout14percentofpatients,asopposedto3percenttaking

placebowithl-dopa.Thiswasofsufficientseveritytocausediscontinuationoftreatmentinabout3percentofthose

enrolled.Tolerancetothisuntowardeffectwasnotobserved.Pergolideshouldonlybeadministeredwithcautionin

patientswithahistoryofpsychosis,sincepre-existingstatesofconfusionandhallucinationmaybeexacerbated.

StudyFindingsintheElderly

Intheplacebo-controlledtrial,2of187patientstreatedwithplacebodied,ascomparedwith1of189patientstreated

withpergolidemesilate.Ofthe2,299patientstreatedwithpergolidemesilateinpre-marketingstudiesevaluatedin

October1988,6.2percentdiedwhileonthedrugorshortlyafterdiscontinuation.Thepatientpopulationunder

evaluationwaselderly,illandathighriskfordeath.Acase-by-casereviewofthepatientswhodiedfailedtodisclose

anyuniquesetofsigns,symptoms,orlaboratoryresultsthatwouldsuggestthattreatmentwithpergolidecausedthese

deaths.

CardiacDisease/Arrhythmia

Cautionshouldbeexercisedwhenadministeringpergolidetopatientspronetocardiacdysrhythmiasorwithsignificant

underlyingcardiacdisease.

Inaplacebo-controlledstudy,patientstakingpergolidemesilatehadsignificantlymoreepisodesofatrialpremature

contractions(APCs)andsinustachycardia

Somnolence

Pergolidehasbeenassociatedwithsomnolenceandepisodesofsuddensleeponset,particularlyinpatientswith

Parkinson’sdisease.Suddenonsetofsleepduringdailyactivities,insomecaseswithoutawarenessorwarningsigns,

hasbeenreportedrarely.Patientsmustbeinformedofthisandadvisedtoexercisecautionwhiledrivingoroperating

machinesduringtreatmentwithpergolide.

Patientswhohaveexperiencedsomnolenceand/oranepisodeofsuddensleeponsetmustrefrainfromdrivingor

operatingmachines.Furthermore,areductionofdosageorterminationoftherapymaybeconsidered.

Patientsshouldbeadvisedtotelltheirdoctoriftheybecomepregnantorintendtobecomepregnantduringtherapy.

Theyshouldalsotelltheirdoctoriftheyarebreastfeeding.

Pathologicalgambling,increasedlibidoandhypersexuality

Pathologicalgambling,increasedlibidoandhypersexualityhavebeenreportedinpatientstreatedwithdopamine

agonistsforParkinson’sdisease,includingpergolide.

Patientswithrarehereditaryproblemsofgalactoseintolerance,theLapplactasedeficiencyorglucose-galactose

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4.5Interactionwithothermedicinalproductsandotherformsofinteraction

Useinpatientsonl-dopamaycauseand/orexacerbatepre-existingstatesofdyskinesia,confusionandhallucinations

(seesection4.4,Specialwarningsandspecialprecautionsforuse).Abruptdiscontinuationofpergolidemesilate,in

patientsreceivingitchronicallyasanadjuncttol-dopa,mayprecipitatetheonsetofhallucinationsandconfusion;these

mayoccurwithinaspanofseveraldays.Discontinuationofpergolideshouldbeundertakengradually,evenifthe

patientistoremainonl-dopa.

Druginteractions:Dopamineantagonists,suchastheneuroleptics(phenothiazines,butyrophenones,thioxanthines)or

metoclopramide,ordinarilyshouldnotbeadministeredconcurrentlywithpergolidemesilate(adopamineagonist);

theseagentsmaydiminishtheeffectivenessofpergolidemesilate.

Becausepergolidemesilateisapproximately90percentassociatedwithplasmaproteins,cautionshouldbeexercisedif

itisco-administeredwithotherdrugsknowntoaffectproteinbinding.

Therearenostudiesinvolvingtheconcomitantadministrationofpergolideandwarfarin.Whenthesetwodrugsareco-

prescribed,carefulmonitoringofanticoagulationshouldbeperformed,withadjustmentsofdosageasnecessary.

Becauseoftheriskofposturaland/orsustainedhypotensioninpatientstakingpergolide,cautionshouldbeexercisedif

itisco-administeredwithantihypertensiveagents.

4.6Pregnancyandlactation

Pregnancy:Inanimalstudiestherewasnoevidenceofharmtothefoetusduetopergolidemesilate.Thereare,

however,noadequateandwell-controlledstudiesinpregnantwomen.Inpre-marketingstudiesofwomenwho

receivedpergolideforendocrinedisorders,therewere33pregnanciesthatresultedinhealthybabiesand6pregnancies

thatresultedincongenitalabnormalities,althoughacausalrelationshiphasnotbeenestablished.Thisdrugshouldbe

usedduringpregnancyonlyifclearlyneeded.

Nursingmothers:Itisnotknownwhetherpergolideisexcretedinhumanmilk.Thepharmacologicalactionof

pergolidesuggeststhatitmayinterferewithlactation.Becausemanydrugsareexcretedinhumanmilkandbecauseof

thepotentialforseriousadversereactionstopergolideinnursinginfants,adecisionshouldbemadewhetherto

discontinuenursingortodiscontinuethedrug,takingintoaccounttheimportanceofthedrugtothemother.

4.7Effectsonabilitytodriveandusemachines

Patientsbeingtreatedwithpergolideandpresentingwithsomnolenceand/orsuddensleepepisodesmustbeinformed

torefrainfromdrivingorengaginginactivitieswhereimpairedalertnessmayputthemselvesorothersatriskof

seriousinjuryordeath(e.g.operatingmachines)untilsuchrecurrentepisodesandsomnolencehaveresolved(seealso

Section4.4,Specialwarningsandprecautionsforuse).

4.8Undesirableeffects

Monotherapy

Thetypesofadverseeventsobservedforpergolideasmonotherapygenerallyreflectthoseseenwhenpergolideisused

asadjunctivetreatmenttolevodopa(seebelow).

Inclinicaltrialsofpergolideasmonotherapy,theoverallreportedincidenceofnauseawashigherthanwasreportedin

trialsofpergolideasadjunctivetherapy.Overall,only3.2percentofpatientsdiscontinuedduetonauseaornauseaand

vomiting.However,theincidenceofdyskinesia,hallucinationsanddizzinesswaslowerinmonotherapytrialsin

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Adjunctivetreatment

Thefollowingadverseevents,whicharelistedindecreasingorderoffrequencyunderbodysystem,wereobserved

duringplacebo-controlledclinicaltrialsatafrequencyofonepercentorgreaterandatasignificantlyhigherincidence

thanplacebo(Pvalue<0.05):

Bodyasawhole:Pain,abdominalpain.

Digestivesystem:Nausea,vomiting,dyspepsia.

Nervoussystem:Dyskinesia,hallucinations,somnolence.Pergolideisassociatedwithsomnolenceandhasbeen

associatedrarelywithexcessivedaytimesomnolenceandsuddensleeponsetepisodes.

Respiratorysystem:Rhinitis,dyspnoea.

Specialsenses:Diplopia.

CardiacDisorders:Verycommon:cardiacvalvulopathy(includingregurgitation)andrelateddisorders(pericarditisand

pericardialeffusion).

Therehavebeenreportsoffibroticandserosalinflammatoryconditions,suchaspleuritis,pleuraleffusion,pleural

fibrosis,pulmonaryfibrosis,pericarditis,pericardialeffusion,cardiacvalvulopathy(includingrestrictivevalvularheart

diseaseandpulmonaryhypertension)andretroperitonealfibrosis,inpatientstakingpergolide(seesection4.4,Special

warningsandprecautionsforuse).Theincidenceofvalvulopathywithpergolideisnotknown,howeverbasedon

recentstudiesoftheprevalenceofvalvularregurgitation(themostsensitiveechocardiographicmarkerforrestrictive

valvulopathy),theprevalenceofregurgitation(virtuallyallcasesasymptomatic)potentiallyattributabletopergolide

maybeinrangeof20percentorgreater.

Thereislimitedinformationavailableonthereversibilityofthesereactions.

Othereventsthathavebeenreportedincludeinsomnia,confusion,dizziness,constipation,diarrhoea,abnormalliver

functiontests,posturalhypotension,syncope,palpitation,atrialprematurecontractions,sinustachycardia,peripheral

vasospasm,rash,fever,Raynaudsphenomenonandneurolepticmalignantsyndrome(withrapiddetitrationof

pergolide),bloodcreatinephosphokinaseincreased(intheabsenceofNMS).Hiccupsanderythromelalgia(warm,red,

painfulswellingoftheextremities)havealsobeenreported.

Themorecommoneventsthatcauseddiscontinuationwererelatedtothenervoussystem,primarilyhallucinationsand

confusion.

PatientstreatedwithdopamineagonistsfortreatmentofParkinson’sdisease,includingpergolide,especiallyathigh

doses,havebeenreportedasexhibitingsignsofpathologicalgambling,increasedlibidoandhypersexuality,generally

reversibleuponreductionofthedoseortreatmentdiscontinuation.

4.9Overdose

Thereisnoclinicalexperiencewithmassiveoverdosage.Overdosesof60mgononeday,19mg/dayfor3days,or

14mg/dayfor23dayshaveoccurred.Symptomsandsignsincludedvomiting,hypotension,agitation,severe

hallucinations,severeinvoluntarymovementsandtinglingsensations.

Anotherpatientwhoinadvertentlyreceived7mg,insteadoftheprescribed0.7mg(700micrograms),experienced

palpitations,hypotensionandventricularextrasystoles.Thehighestdailydose(prescribedforseveralpatientswith

refractoryParkinson'sdisease)hasexceeded30mg.

Inanimals,manifestationsofoverdosageincludenausea,vomiting,convulsions,decreasedbloodpressureandCNS

stimulation.

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Arterialbloodpressureshouldbemaintained.Anantiarrhythmicagentmaybenecessary.IfsignsofCNSstimulation

arepresent,aphenothiazine,orotherbutyrophenoneneurolepticagent,maybeindicated.

Activatedcharcoalmaybeconsideredinsteadof,orinadditionto,gastricemptying.

Dialysisorhaemoperfusionareunlikelytobeofbenefit.

5PHARMACOLOGICALPROPERTIES

5.1Pharmacodynamicproperties

PergolidemesilateisapotentergotderivativedopaminereceptoragonistatD DandDreceptorsites.Pergolideis

10to1,000-timesmorepotentthanbromocriptineonamilligrampermilligrambasisinvariousinvitroandinvivo

testsystems.Pergolidemesilateinhibitsthesecretionofprolactininhumansandlowersserumprolactin

concentrations;itcausesatransientriseinserumconcentrationsofgrowthhormoneandadecreaseinserum

concentrationsofluteinizinghormone.

InParkinson'sdisease,pergolidemesilateisbelievedtoexertitstherapeuticeffectbydirectlystimulatingpostsynaptic

dopaminereceptorsinthenigrostriatalsystem.

5.2Pharmacokineticproperties

Studiesinmalehealthyvolunteershaveshownthatpergolideappearstobeactiveatthepituitary,asmeasuredby

attenuationofplasmaprolactinlevels,2hourspostdosing.Suppressionofprolactinfollowingadoseof50

microgramsmaybecompleteandcanlastforatleast24hours.InParkinson’sdiseasepatients,pergolideappearstobe

activeatthepituitarywithin30minutesoforaldosing,asmeasuredbytimetoattenuationofplasmaprolactinlevels.

Completesuppressionofprolactinoccurs2hourspostdose.

Followingoraladministrationof Cradiolabelledpergolidemesilatetohealthysubjects,approximately55percentof

theadministeredradioactivitycanberecoveredaspergolidemetabolitesfromtheurine,40percentfromthefaecesand

5percentfromexpiredCO,suggestingthatasignificantfractionisabsorbed.Nothingcanbeconcludedaboutthe

extentofpresystemicclearance,ifany.

Dataonpostabsorptiondistributionofpergolideareunavailable.

Inhumans,pergolideismetabolisedextensively.Atleast10metaboliteshavebeendetected,includingN-

despropylpergolide,pergolidesulfoxide,andpergolidesulfone.Pergolidesulfoxideandpergolidesulfoneare

dopamineagonistsinanimals.Theotherdetectedmetaboliteshavenotbeenidentifiedanditisnotknownwhetherany

othermetabolitesareactivepharmacologically.

Themajorrouteofexcretionisviathekidney.

Becausepergolidemesilateisapproximately90percentassociatedwithplasmaproteins,cautionshouldbeexercisedif

itisco-administeredwithotherdrugsknowntoaffectproteinbinding.

5.3Preclinicalsafetydata

Carcinogenesis,mutagenesisandimpairmentoffertility:Twoyearcarcinogenicitystudiesinmiceandratsuseddoses

upto340and12timesthemaximumhumanoraldose(6mgor6000micrograms/dayequivalentto120

micrograms/kg/day).Alowincidenceofuterineneoplasmsoccurredinbothratsandmice.Endometrialadenomas

andcarcinomaswereobservedinrats.

Endometrialsarcomaswereobservedinmice.Theseoccurrencesareprobablyattributabletothehigh

oestrogen/progesteroneratio,whichwouldoccurinrodentsasaresultoftheprolactin-inhibitingactionofpergolide

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Furthermore,noincreasedriskofuterinemalignancieshasbeenidentifiedamongpatientsreceivingpergolide.

Mutagenicpotentialwasevaluatedinabatteryoftests.Aweakresponsewasnotedinonetest,amammaliancell-

point-mutationassay,onlyaftermetabolicactivationwithratlivermicrosomes,buttheotherfivetestswerenegative.

Therelevancetohumansisunknown.

Impairedfertilitywasobservedinmiceatthehighestdose(5.6mgor5600micrograms/kg/day).Thismayberelatedto

depressedprolactinlevels.

6PHARMACEUTICALPARTICULARS

6.1Listofexcipients

Lactosemonohydrate

Croscarmellosesodium

Povidone

Magnesiumstearate

Ironoxideyellow(E172)

Methionine

6.2Incompatibilities

Notapplicable.

6.3ShelfLife

2years.

6.4Specialprecautionsforstorage

Donotstoreabove25ºC.Keeptheblisterintheoutercartontoprotectfromlight

6.5Natureandcontentsofcontainer

Blisterpacksof100tablets,withformingmaterialof25micronnylon/40micronaluminium/60micronUPVCand

liddingmaterialof20micronaluminium/5-6gmsclearheat-sealingcoating.

StarterPack(adjunctivetreatment):81tabletscontaining75x50microgramtabletsand6x250microgramtablets.

StarterPack(monotherapy):166tabletscontaining109x50microgramtabletsand57x250microgramtablets.

Notallpacksizesmaybemarketed.

6.6Specialprecautionsfordisposalofausedmedicinalproductorwastematerialsderivedfrom

suchmedicinalproductandotherhandlingoftheproduct

Donotcrushtablets.Cautionisadvisedtominimiseexposureriskswhensplittingtablets.Inspontaneouscases,reports

ofeyeirritation,irritatingsmell,orheadachewhenpergolidetabletsweresplitorcrushedhavebeenidentified.In

animalstudies,pergolidewasfoundtocauseeyeirritationandinhalationtoxicity.Intheeventofpergolidepowder

exposuretothetheeye,theaffectedeyeshouldbeflushedimmediatelywithwater,andmedicaladviceobtained.For

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7MARKETINGAUTHORISATIONHOLDER

EliLillyandCompanyLimited

LillyHouse

PriestleyRoad

Basingstoke

Hampshire

RG249NL

UnitedKingdom

8MARKETINGAUTHORISATIONNUMBER

PA0047/073/001

9DATEOFFIRSTAUTHORISATION/RENEWALOFTHEAUTHORISATION

Dateoffirstauthorisation:18October1993

Dateoflastrenewal:18October2008

10DATEOFREVISIONOFTHETEXT

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